Linda E.A. Kanim

Somatosensory evoked potential spinal cord monitoring reduces neurologic deficits after scoliosis surgery: results of a large multicenter survey

Neurologic deficits were compared to somatosensory evoked potential (SEP) spinal cord monitoring in a survey of spinal orthopedic surgeons. Experienced SEP spinal cord monitoring teams had fewer than one-half as many neurologic deficits per 100 cases compared to teams with relatively little monitoring experience. Experienced SEP monitoring teams also had fewer neurologic deficits than were seen in previous surveys of this group. Definite neurologic deficits, despite stable SEPs (false negative monitoring), occurred during surgery in only 0.063% of patients. Factors independently associated with fewer neurologic deficits also included the surgeons years of experience in orthopedic surgery and the use of the wake-up test. Other technical survey results are also presented here. These results confirm the clinical efficacy of experienced SEP spinal cord monitoring for prevention of neurologic deficits during spinal surgery such as for scoliosis.

Spinal fusion in the United States: analysis of trends from 1998 to 2008.

Study Design. Epidemiological study using national administrative data. Objective. To provide a complete analysis of national trends in spinal fusion from 1998 to 2008 and compare with trends in laminectomy, hip replacement, knee arthroplasty, percutaneous transluminal coronary angioplasty, and coronary artery bypass graft. Summary of Background Data. Previous studies have reported a rapid increase in volume of spinal fusions in the United States prior to 2001, but limited reports exist beyond this point, analyzing all spinal fusion procedures collectively. Methods. Data were obtained from the Healthcare Cost and Utilization Project Nationwide Inpatient Sample for the years 1998 to 2008. Discharges were identified using International Classification of Diseases, Ninth Revision, Clinical Modification procedure codes for the following procedures: spinal fusion, laminectomy, hip replacement, knee arthroplasty, percutaneous transluminal coronary angioplasty, and coronary artery bypass graft. Population-based utilization rates were calculated from the US census data. Results. Between 1998 and 2008, the annual number of spinal fusion discharges increased 2.4-fold (137%) from 174,223 to 413,171 (P < 0.001). In contrast, during the same time period, laminectomy, hip replacement, knee arthroplasty, and percutaneous coronary angioplasty yielded relative increases of only 11.3%, 49.1%, 126.8%, and 38.8% in discharges, while coronary artery bypass graft experienced a decrease of 40.1%. Between 1998 and 2008, mean age for spinal fusion increased from 48.8 to 54.2 years (P < 0.001), in-hospital mortality rate decreased from 0.29% to 0.25% (P < 0.01), and mean total hospital charges associated with spinal fusion increased 3.3-fold (P < 0.001). The national bill for spinal fusion increased 7.9-fold (P < 0.001). Conclusion. Frequency, utilization, and hospital charges of spinal fusion have increased at a higher rate than other notable inpatient procedures, as seen in this study from 1998 to 2008. In addition, patient demographics and hospital characteristics changed significantly; in particular, whereas the average age for spinal fusion increased, the in-hospital mortality rate decreased.

Increased fusion rates with cervical plating for three-level anterior cervical discectomy and fusion.

Study Design. A retrospective review of all patients surgically treated by a single surgeon with a three-level anterior cervical discectomy and fusion with and without anterior plate fixation. Objectives. To compare the clinical and radiographic success of anterior three-level discectomy and fusion performed with and without anterior cervical plate fixation. Summary of Background Data. Previous studies of multilevel cervical discectomies and fusions have shown fusion rates to decrease as the number of surgical levels increases. Anterior cervical plate stabilization can provide more stability and may increase fusion rates for multilevel fusions. Methods. Over a 7-year period, 59 patients were treated surgically with a three-level anterior cervical discectomy and fusion by the senior author. Forty patients had cervical plates, whereas 19 had fusions with no plates. These patients were observed for an average of 3.2 years. Clinical and radiographic follow-up data were obtained. Results. Of the 59 patients, 14 had a pseudarthrosis (7 in each group). The pseudarthrosis rates were 18% (7 of 40) for patients with plating and 37% (7 of 19) for patients with no plating. Although the nonunion rate for unplated fusions was double that of plated fusions, this difference was not statistically significant. There was no statistically significant correlation between pseudarthrosis and gender, age, level of surgery, history of tobacco use, or previous anterior surgery. The fusion rates were improved with the use of a cervical plate. Inferior clinical results were demonstrated in patients with a pseudarthrosis, regardless of the use of a cervical plate. Conclusions. The addition of plate fixation for three-level anterior cervical discectomy and fusion is a safe procedure and does not result in higher complication rates. In this study, the pseudarthrosis rate was lower for patients with a cervical plate. However, this difference was not statistically significant. Patients treated with cervical plating had overall better results when compared with those of patients treated without cervical plates. Although the use of cervical plates decreased the pseudarthrosis rate, a three-level procedure is still associated with a high nonunion rate, and other strategies to increase fusion rates should be explored.

Spinal Cord Monitoring: Results of the Scoliosis Research Society and the European Spinal Deformity Society Survey

The Scoliosis Research Society (SRS) and the European Spinal Deformity Society (ESDS) membership was surveyed regarding the use of intraoperative monitoring of somatosensory evoked potentials in spinal surgery. A total of 242 people responded, with 188 using intraoperative monitoring. A second survey was distributed detailing the technical aspects of monitoring, of which 71 were returned. A total of 342 neurologic deficits were reported to have occurred with monitoring in place. Two hundred forty-six (72%) were accurately detected, and 96 (28%) were not detected by sensory cord evoked potentials (SCEP). There were 1,003 false-positive cases reported. The incidence of false-negative cases was related to those not monitoring both latency and amplitude, to using fewer recording electrodes, and with those surgeons doing more kyphosis corrections.

Effective doses of recombinant human bone morphogenetic protein-2 in experimental spinal fusion.

Study Design Nineteen dogs underwent L4‐L5 intertransverse process fusions with either 58 μg, 115 μg, 230 μg, 460 μg, or 920 μg of recombinant human bone morphogenetic protein‐2 carried by a polylactic acid polymer. A previous study (12 dogs) compared 2300 μg of recombinant human bone morphogenetic protein‐2, autogenous iliac bone, and carrier alone in this model. All fusions subsequently were compared. Objectives To characterize the dose‐response relationship of recombinant human bone morphogenetic protein‐2 in a spinal fusion model. Summary of Background Data Recombinant osteoinductive morphogens, such as recombinant human bone morphogenetic protein‐2, are effective in vertebrate diaphyseal defect and spinal fusion models. It is hypothesized that the quality of spinal fusion produced with recombinant human bone morphogenetic protein‐2, above a threshold dose, does not change with increasing amounts of inductive protein. Methods After decortication of the posterior elements, the designated implants were placed along the intertransverse process space bilaterally. The fusion sites were evaluated after 3 months by computed tomography imaging, high‐resolution radiography, manual testing, mechanical testing, and histologic analysis. Results As in the study using 2300 μg of recombinant human bone morphogenetic protein‐2, implantation of 58–920 μg of recombinant human bone morphogenetic protein‐2 successfully resulted in intertransverse process fusion in the dog by 3 months. This had not occurred in animals containing autograft or carrier alone. The cross‐sectional area of the fusion mass and mechanical stiffness of the L4‐L5 intersegment were not dose‐dependent. Histologic findings varied but were not related to rhBMP‐2 dose. Inflammatory reaction to the composite implant was proportional inversely to the volume of the fusion mass. Conclusions No mechanical, radiographic, or histologic differences in the quality of intertransverse process fusion resulted from a 40‐fold variation in dose of recombinant human bone morphogenetic protein‐2.

ProDisc artificial total lumbar disc replacement: introduction and early results from the United States clinical trial.

Study Design. Multicenter prospective randomized study of artificial disc replacement (ProDisc) versus circumferential fusion (standard of care) for one- and two-level degenerative disc disease. This is an interim analysis on patients seen at the Spine Institute Saint John’s Health Center, Santa Monica, California. Objectives. To evaluate early pain and functional outcomes of patients treated with disc replacement or fusion and to assess the capacity of this intervertebral disc replacement for preserving motion in the lumbar spine. Summary of Background Data. Disc replacement is intended to reduce pain via removal of the diseased disc while restoring physiologic motion and height at the affected level. The long-term physiologic advantage of disc replacement to fusion is that preservation of motion may prevent additional degeneration at adjacent levels. Methods. Patients meeting inclusion criteria were consented for study. Randomization was performed using a 2 to 1 ratio of disc replacement procedure to a fusion procedure. Patients rated their pain on the Visual Analogue Scale and completed the Oswestry Disability Index questionnaire. Radiographs were taken. Assessments were made before surgery and after surgery at 6 weeks, 3 months, 6 months, and 1 year (ongoing). Changes from preoperative pain, disability, or motion were separately evaluated as a function of treatment using repeated measures mixed design analysis of variance. Results. This analysis includes data up to 6 months from the first 53 randomized patients. There were 35 patients who underwent disc replacements, and 18 patients had fusion procedures. Disc replacement patients had a significant reduction in pain and disability at earlier evaluations. By 6 months, the relative improvement on both the Visual Analogue Scale and Oswestry (both, P < 0.05) were similar for disc replacement and fusion patients. Greater motion was found at L4–L5 for disc replacement patients (P < 0.05) than fusion patients. A similar trend was noted at L5–S1 (P was not significant). Conclusions. Disc replacement patients reported significantly less pain (Visual Analogue Scale) and disability (Oswestry) in the early period following surgery compared to fusion patients. This difference disappeared by 6 months. When compared to fusion, the disc replacement allowed preservation of motion at L4–L5 with a similar trend at L5–S1.

Evaluation of rhBMP-2 with an OPLA carrier in a canine posterolateral (transverse process) spinal fusion model.

Study Design Posterolateral L4-L5 transverse process fusions were done on 14 adult beagles. Six were implanted with recombinant human bone morphogenetic protein-2 carried by open-cell polylactic acid polymer delivery vehicle. Six received autogenous iliac bone graft. Two received carrier alone. Eleven were killed 3 months after implantation. One in each group was maintained for 8 months. Objectives. To compare recombinant human bone morphogenetic protein-2 and open-cell polylactic acid polymer with autogenous iliac bone for inducing transverse process fusion in the canine by 3 months and to determine whether transverse process decortication and implantation of carrier alone causes spontaneous transverse process fusion in the canine. Summary of Background Data Recombinant human bone morphogenetic proteins have healed segmental long bone defects in several models. They have induced interlaminar and facet fusions in canines. Interlaminar and facet fusions have occurred after sham decortications in canines. Recombinant human bone morphogenetic protein-2 has not been evaluated for transverse process fusion in canines. Transverse process fusion is a preferred clinical method for achieving posterior lumbar fusion. Methods Fusion sites were evaluated by serial computed tomography scans. After the dogs were killed, explanted spines were subjected to manual testing, mechanical testing, high resolution radiography, and histologic analysis. Results One hundred percent of recombinant human bone morphogenetic protein-2-implanted sites had solid transverse process fusion by 3 months according to all measures. No autografted sites were fused at this interval. Osseous bridging of posterolateral gutters occurred in the recombinant human bone morphogenetic protein-2-implanted sites after 2 months, the earliest radiographic measure. None of the carrier-only sites showed bone formation. Conclusions Recombinant bone morphogenetic protein-2 carried by open-cell polylactic acid polymer is superior to autogenous iliac bone for producing radiographically and mechanically solid transverse process fusions in canines by 3 months. Spontaneous transverse process fusion does not occur in canines after decortication and open-cell polylactic acid polymer implantation.

The effect of cervical plating on single-level anterior cervical discectomy and fusion.

The use of anterior plates for single-level cervical fusions is controversial. Previous studies that evaluated single and multiple-level fusions have shown increased and decreased fusion rates when cervical plates are used. The purpose of this study was to compare the clinical and radiographic success of single-level discectomy performed with and without anterior cervical plate fixation. During a 6-year period, 80 patients were surgically treated with a single-level anterior cervical discectomy. Forty-four patients had cervical plates, whereas 36 had fusions without plates (average follow-up, 2.3 years). The pseudarthrosis rates were 4.5% (2 of 44) for patients with plating and 8.3% (3 of 36) without plating. This difference was not significant (p = 0.653). There was no correlation of pseudarthrosis with sex, age, level of surgery, history of tobacco use, or the presence of previous anterior surgery. The amount of graft collapse for patients with plating was 0.75 mm compared with 1.5 mm for those without a plate (p = 0.026). The amount of kyphotic deformity of the fused segment was 1.2 degrees with plating compared with 1.9 degrees for patients without plating (p = 0.079). Ninety-one percent of the patients with plating had good or excellent results compared with 88% in the group without cervical plates, based on Odoms criteria. The addition of plate fixation for single-level anterior cervical discectomy and fusion is safe and not associated with a significant increase in complication rates. The pseudarthrosis rates are not significantly different when a cervical plate is used.

Effect of Regional Gene Therapy with Bone Morphogenetic Protein-2-Producing Bone Marrow Cells on Spinal Fusion in Rats

Background: Bone morphogenetic proteins (BMPs) are now being used as bone-graft substitutes to enhance spinal fusion. However, the large doses of BMP required to induce a spinal fusion in humans suggests that the delivery of these proteins should be improved. We used ex vivo adenoviral gene transfer to create BMP-2-producing bone marrow cells, and these autologous cells were found to induce a posterolateral fusion of the spine in syngeneic rats. Methods: Intertransverse spinal arthrodesis (L4 and L5) was attempted in ten groups of Lewis rats with 5 × 10 6 BMP-2-producing rat bone marrow cells (Ad-BMP-2 cells), created through adenoviral gene transfer with guanidine hydrochloride-extracted demineralized bone matrix as a carrier (Group I); 5 × 10 6 Ad-BMP-2 cells on a collagen sponge carrier (Group II); 10 &mgr;g of recombinant BMP-2 (rhBMP-2) in a guanidine hydrochloride-extracted demineralized bone matrix carrier (Group III); 10 &mgr;g of rhBMP-2 in a collagen sponge carrier (Group IV); autogenous iliac crest bone-grafting (Group V); 5 × 10 6 &bgr;-galactosidase-producing rat bone marrow cells, created through adenoviral gene transfer with guanidine hydrochloride-extracted demineralized bone matrix as a carrier (Group VI); decortication of the transverse processes alone (Group VII); 5 × 10 6 uninfected rat bone marrow cells with a guanidine hydrochloride-extracted demineralized bone matrix carrier (Group VIII); guanidine hydrochloride-extracted demineralized bone matrix only (Group IX); or a collagen sponge alone (Group X). Each specimen underwent plain radiography, manual palpation, and histological analysis. Results: All spines in Groups I and II (BMP-2-producing bone marrow cells) and all spines in Groups III and IV were fused at four weeks postoperatively. In contrast, none of the spines in the other groups had fused at a minimum of eight weeks after implantation. Histological analysis of the specimens revealed that the spines that had received BMP-2-producing bone marrow cells (Groups I and II) were filled with coarse trabecular bone postoperatively, whereas those that had received rhBMP-2 (Groups III and IV) were filled with thin, lace-like trabecular bone. All of the other spines, including those that had been treated with autogenous iliac crest bone-grafting (Group V), produced little or no new bone. Conclusion: BMP-2-producing bone marrow cells, created by adenoviral gene transfer, produce sufficient BMP to induce an intertransverse fusion in the rat spine model. Clinical Relevance: Regional gene therapy can be used to induce spinal fusion. This strategy with use of transduced bone marrow cells created through ex vivo gene transfer with a BMP-2-containing adenovirus could be adapted to enhance spinal fusion in humans.

Experimental spinal fusion with recombinant human bone morphogenetic protein-2 without decortication of osseous elements

Study Design. L4-L5 intertransverse process fusions were produced with 58 μg, 230 μg, or 920 μg of recombinant human bone morphogenetic protein-2 in 20 dogs. Eleven had traditional decortication of posterior elements before insertion of the implant. Nine were left undecorticated. All animals were evaluated 3 months after surgery. Objectives. To determine whether decortication is a prerequisite for successful fusion in the presence of osteoinductive proteins such as bone morphogenetic protein-2. Summary of Background Data. Recombinant osteoinductive proteins can induce de novo bone in ectopic soft-tissue sites in the absence of bone marrow elements. Traditional methods for achieving spinal fusion rely on exposure of bone marrow through decortication to facilitate osteogenesis. It is hypothesized that the presence of an implanted osteoinductive protein obviates the need for exposure and release of host inductive factors. Methods. Recombinant human bone morphogenetic protein-2-induced intertransverse process fusions were performed with and without decortication. Fusion sites were evaluated by computed tomography imaging, high-resolution radiography, manual testing, mechanical testing, and histologic analysis. Results. One hundred percent of decorticated spines and 89% of undecorticated spines were clinically fused by 3 months. Ninety-one percent of decorticated spines and 78% of undecorticated specimens exhibited bilateral transverse process osseous bridging. The only spines that failed to achieve solid bilateral arthrodesis were in the lowest dose group. With the higher two doses, there was histologic evidence of osseous continuity between the fusion mass and undecorticated transverse processes. Conclusions. There were no statistical differences in clinical and radiographic fusion rates between decorticated and undecorticated sites. With higher doses of recombinant human bone morphogenetic protein-2, there was little histologic distinction between fusions in decorticated versus undecorticated spines.